The genus Candida, especially Candida albicans, is currently the most prevalent etiologic agent of systemic mycoses. However, since 1980, several epidemiological analyses have documented the growing impact of outbreaks caused by “non-C. albicans” species in the bloodstream; it is the case of C. glabrata in the US and C. parapsilosis and C. tropicalis in Europe, Canada and Latin America. Although considered less virulent than C. albicans these species of Candida have great clinical impact, especially affecting immunity compromised patients or those weakened by invasive surgery and prolonged treatment with antibiotics.
The species of Candida, which have been the subject of general research, and so far have failed to be combated effectively by naturally occurring compounds, are those listed below:                Candida parapsilopsis         Candida glabrata         Candida tropicalis         Candida krusei         Candida dubliniensis         Candida guillermondi         Candida lusitaniae         
C. albicans being the most virulent and therefore the scientific community should focus more efforts on it to combat it effectively.
C. albicans 
The yeast Candida albicans is defined as an imperfect fungus whose habitat is obligatorily associated with humans and other warm-blooded animals. Taxonomic studies of sequence homology and analysis of physiological and phenotypic similarities situate C. albicans within the group of ascomycete yeasts with no real sexual cycle. The genus Candida is primarily characterised in that it includes species with unpigmented colony morphology, reference to which is made under the species name of “albicans”, being this absence of pigmentation made visible by means of caretenoid compounds. They are able to use carbohydrates through fermentation and grow in the temperature range of mesophilic microorganisms (25-42° C.). As the main hydrocarbon reserve, it accumulates glycogen and also synthesises trehalose, whose content varies depending on the growth phase.
However, the biological activity of C. albicans differs substantially in two essential aspects from the rest of the ascosporogenic saprophytic yeasts, exemplified through Saccharomyces cerevisiae by:                Its required association with homeothermic animals, as mentioned.        Its status as an imperfect fungus, lacking real natural sexual cycle. C. albicans is a permanent diploid and therefore is obliged to divide by asexual reproduction. This property carries an additional difficulty for genetic analysis, although in recent years considerable progress has been made in the development of new molecular tools.Clinical Significance        
Candida albicans is considered the most prevalent opportunistic pathogenic microorganism in the human species. It is a common fungus of the commensal flora in healthy individuals, causing both superficial and systemic infections in the oral mucosa, digestive system or vaginal tract. As a commensal organism, it lives in harmless equilibrium with its host. However, C. albicans becomes a very virulent pathogen when the immune system is lowered or is severely weakened, being very frequent the occurrence of invasive candidiasis in AIDS sufferers, diabetics, patients undergoing intensive surgery or transplant recipients, infants, the elderly and persons subject to antitumor antibiotic therapy or prolonged treatment.
Superficial and Systemic Candidiasis
Infections caused by various species of the genus Candida are named candidiasis. Although C. albicans is the most important, other common species such as C. tropicalis, C. glabrata, C. krusei, C. dubliensis and C. lusitaniae, are often isolated in clinical samples as highly virulent pathogens. The candidiasis can be of two types:
Superficial: Affecting primarily the skin and mucous membranes of the oral and vaginal cavities, sometimes extending to the nails and scalp
Systemic: In this case, the cells of the pathogen proliferate extensively in the blood, affecting one or more vital organs and generally causing symptoms of septicemia (or candidemia).
The clinical incidence of this opportunistic fungus has increased in recent years with an increasing segment of the population having altered immune defences, and it is equally a major health problem of hospital-associated type infections.
Virulence Factors
Interactions between parasite and host are an essential pathogenicity factor. Thus, factors of virulence in C. albicans are considered as all the genetic and physiological characteristics relating to its ability to cause infection to the host, to resist antifungal therapy, or to damage the cells and tissues that it invades. Among the virulence factors of C. albicans stand out:                The hydrophobicity of the cell surface.        The synthesis of molecules involved in the host adhesion.        The formation of biofilms on prostheses or catheters.        The secretion of hydrolytic enzymes.        The mycelium-yeast dimorphic change and other phenotypic changes (“switching”).Antifungal Susceptibility        
The treatment with conventional specific antifungals, such as azoles (ketoconazole or fluconazole) and amphotericin B have only proven useful in reducing (oropharyngeal, oesophageal or vaginal) mucocutaneous candidiasis and cryptococcosis in patients with AIDS. However, in the case of generalised candidiasis, routine administration of these drugs is not recommended because its absorption is poor, its effectiveness limited and it tends to favour the emergence of resistant strains.
The search for new antifungal substances endowed with both potent pharmacological action and selective high toxicity is an urgent clinical need, due to the dramatic increase in systemic and hospital-associated fungal infections. Epidemiological data show how the incidence of total hospital-associated infections has increased 10 times (candidiasis represents 17% on the total) in the past five years, and numerous cases of affected immunocompromised patients have been reported.
The main research efforts are aimed at finding new antifungal targets. The study of the cell wall has been given great attention and thus the clinical use of a new antifungal agent of the Echinocandins family, which act as specific inhibitors of glucan synthase, involved in the synthesis of β-(1,3)-glucan, the main component of the cell wall, has already been approved. Early evidence shows that the application of caspofungin to invasive candidiasis achieves a similar efficacy to the treatments with fluconazole or liposomal amphotericin B, but with a much higher tolerability.
Although active ingredients from natural extracts such as: Cuminum cyminum, Salvadora persica, Syngonanthus nitens, Tulbaghia alliacea, Alternaria alternata, Trichoderma spp., Arthrinium arundinis, Selaginella tamariscina, Glycyrrhizine and Citrus bergamia, have been studied in various scientific experiments, none of them have proved to be an effective antifungal agent against Candida infections.
In the research world and the application thereof to existing pathologies in the matter at hand, there are some gaps in implementation and effectiveness.
In this sense, we could say that in the present state we find that each condition is sectorally and individually treated, so that the active ingredient used to try to combat pyorrhoea is different from that used for treating candidiasis and caries or the Streptococcus mutans. 
The solutions offered are, on one hand, unilateral and segmented for each condition and, on the other hand, the active ingredients offered disregard comprehensive losses of functionality. Furthermore, there is no patented product that fully combats candidiasis, as each unique active ingredient or combination conceived to this purpose has failed in its noble and laudable goal of eliminating the disease.
The design of an effective strategy against the pernicious activity of the Candida species described in the various conditions mentioned requires a twofold understanding, on the one hand molecular and multitarget on the other. The random combination of natural extracts or products does not lead in any case to the achievement of positive, appropriate results applicable in clinical reality.
Labiatae are a peculiar and large family of angiosperm plants and shrubs characterized by having a square stem, opposing and decussate leaves, hermaphrodite flowers, often zigomorphs, brightly coloured, persistent calyx with firmly united corolla petals (gamopetal) whose end terminates in two parts or lips (bilabial), formed by two upper and three lower petals. As for its fruit, it is dry and consists of four nutlets. Widely known examples are rosemary, basil, lavender thyme and sage.
The existing literature contains many studies in which compounds from Rosmarinus officinalis (rosemary) are used against candidiasis, but always using the fraction of essential oil containing only monoterpenes: cineol, camphor, borneol, verbenone, etc., and not the polyphenolic fraction containing diterpenes and other compounds such as triterpenes and caffeic acid derivatives.
In our investigations, an extract highly and specifically enriched in diterpenes (concentration of diterpenes higher than 80%) and especially in carnosic acid (carnosic acid concentration higher than 70%) was used, with the additional presence of small proportions of carnosol and other diterpenes of similar structure.
Carnosic acid, whose structure is shown below, is a phenolic diterpene that is extracted from the leaves of the rosemary plant (Rosmarinus officinalis) and its antioxidant, anticancer, neuroprotective and anti-inflammatory properties as well as its preservative effect for products of various kinds, are widely known.
